Our objective is to increase our understanding of the roles and functioning of lysosomes of mammalian tissues, both normal and neoplastic. Accordingly, the proposed project involves studies on 1) lysosomal glycosidases, particularly alpha-D-mannosidases which, interestingly, occur (as different forms) in Golgi membranes and soluble cytoplasm as well as in lysosomal membranes, which must hold keys to understanding the mechanism of formation of lysosomes and to the regulation of vacuole fusion, and 3) the development of an in vitro system which might permit the disclosure of lysosome fusion mechanisms. The studies on glycosidases and on membrane composition are relevant to 1) the membrane glycoprotein abnormalities that often accompany neoplastic transformation, 2) the fate of viruses in mammalian cells, and 3) current effort to develop cancer chemotherapeutic agents which depend on the membrane and vacuolar system of cells.